New Brunswick, NJ, USA. New research identifies the ways the replication of a DNA strand is coordinated by enzymes, resulting in simultaneous copies.

DNA replication is a fundamental process in living organisms, allowing cells to divide and multiply, all while maintaining the genetic code and proper function of the original cell. Two identical DNA molecules are produced from a single double-stranded DNA molecule, providing the basis for biological inheritance. The underlying mechanism presents challenges as the double helical (coil-shaped) DNA divides into two strands duplicated by different methods, yet both strands complete the replication at the same time.

Proofreading and error-checking mechanisms in the cells ensure near perfect fidelity for DNA replication. However, breakdowns in these editing processes can interfere with inheritance, resulting in a variety of genetic and/or developmental anmalies. New research has addressed this fundamental problem. The study identifies three essential ways the synthesis of the two strands is coordinated by enzymes, settling scientific deliberations on how the two DNA strands are copied in the same time span.

“DNA replication is a fundamental reaction required for the maintenance, survival, and propagation of living cells. It is also a very complex reaction that has been studied for decades without a clear understanding of how the two interwound strands are copied at the same time,” says Smita Patel, PhD, RWJMS biochemistry professor and lead author of the paper.

Dr. Patel says “Our study explains how the replication is coordinated — an important piece of the puzzle, because errors in DNA replication can cause disabilities and disease, such as cancer.”

The helicase enzyme initiates DNA replication, by unwinding, or separating, the strands which are then reproduced by polymerase enzymes which are responsible for making an exact copy of the DNA. One strand, called the leading strand, is reproduced continuously, whereas the other, lagging strand is reproduced in fragments that are later joined together. How the two strands are replicated at the same time was not previously understood because the polymerase enzyme that replicates the lagging strand must recycle after the completion of each fragment.

According to Dr. Patel, the researchers used these state-of-the-art methods to measure the progression of DNA synthesis in the millisecond time scale. “We employed rapid kinetic methods to investigate this problem and coupled it with single molecule fluorescence measurements to show that the replication enzymes do not pause, as previously thought, but our studies suggest that the short fragments are synthesized at a slightly faster rate so lagging strand synthesis can keep up with the synthesis of the leading strand that is made continuously,” said Dr. Patel.

These methods captured the replication enzymes in the act of making the DNA and identified the three ways the strands complete replication simultaneously. First, as Dr. Patel noted, the lagging strand polymerase keeps up with the leading strand polymerase by moving a little faster, which gives the lagging polymerase the extra time it needs to recycle and start the synthesis of a new DNA fragment.

This finding supports an early model proposed by Bruce Alberts, a professor emeritus in the department of biochemistry and biophysics at the University of California, San Francisco, former president of the National Academy of Sciences and editor-in-chief of Science magazine.

The study also shows that the reproduction time is further reduced by making the RNA primer ahead of time as the lagging-strand synthesis progresses through the cycle. The RNA primer is a sequence of nucleotides (molecules that, when joined together, make up the structural units of RNA and DNA) copied from DNA.

According to Dr. Patel, the polymerase needs RNA primer to initiate replication of a new fragment and that making it “on the fly” saves time in the replication process. Lastly, the research shows that the RNA primer is kept in physical proximity to the lagging strand polymerase by means of a priming loop so that the polymerase enzyme can access it and begin replication of a new fragment quickly.

Thus, the faster movement of the lagging strand polymerase enzyme, the ability to make the RNA primer ahead of time and the ability for the polymerase enzyme to access the RNA primer quickly due to its close location allow the two strands of the DNA to be copied in the same time span.

The TS-Si News Service is a collaborative effort by TS-Si.org editors, contributors, and corresponding institutions. Sources can include the cited individuals and organizations, as well as TS-Si.org staff contributions. Articles and news reports do not necessarily convey official positions of TS-Si, its partners, or affiliates. We welcome your comments. Use the form below to leave a public comment or send private correspondence via the TS-Si Contact Page. We will not divulge any personal details or place you on a mailing list without your permission.


TS-Si is dedicated to the acceptance, medical treatment, and legal protection of individuals correcting the misalignment of their brains and their anatomical sex, while supporting their transition into society as hormonally reconstituted and surgically corrected citizens.

Tweet

Comments (0)

Subscribe to this comment's feed

Show/hide comments

Show/hide comment form

Name

Email

Website

Title

Comment

smaller | bigger

I have read and agree to the Terms of Usage.

Add Comment